ArticleJournal of clinical microbiology2017
Detection of Isoniazid-, Fluoroquinolone-, Amikacin-, and Kanamycin-Resistant Tuberculosis in an Automated, Multiplexed 10-Color Assay Suitable for Point-of-Care Use.
Article in Journal of clinical microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Xpert MTB/XDR for detection of pulmonary tuberculosis and resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin.The Cochrane database of systematic reviews · 2022Pooled it
- Antibiotic heteroresistance in Mycobacterium tuberculosis isolates: a systematic review and meta-analysis.Annals of clinical microbiology and antimicrobials · 2021Pooled it
- Meta-narrative review of molecular methods for diagnosis and monitoring of multidrug-resistant tuberculosis treatment in adults.International journal of mycobacteriologyPooled it
- A novel one-tube nested fluorescence melting curve analysis for rapid detection of drug-resistant Mycobacterium tuberculosis.BMC microbiology · 2025Article
- Xpert MTB/XDR assay: rapid TB drug resistance detection.Infection · 2024Article
- Article
- Reflex Xpert MTB/XDR Testing of Residual Rifampicin-Resistant Specimens: A Clinical Laboratory-Based Diagnostic Accuracy and Feasibility Study in South Africa.Open forum infectious diseases · 2024Article
- Diagnostic accuracy of the XpertBMC infectious diseases · 2024Article
- Laboratory tools for the direct detection of bacterial respiratory infections and antimicrobial resistance: a scoping review.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2024Article
- Rapid Detection of Extensive Drug Resistance by Xpert MTB/XDR Optimizes Therapeutic Decision-Making in Rifampin-Resistant Tuberculosis Patients.Journal of clinical microbiology · 2023Article
- Quantification of Isoniazid-Heteroresistant Mycobacterium tuberculosis Using Droplet Digital PCR.Journal of clinical microbiology · 2023Article
- Feasibility, Ease-of-Use, and Operational Characteristics of World Health Organization-Recommended Moderate-Complexity Automated Nucleic Acid Amplification Tests for the Detection of Tuberculosis and Resistance to Rifampicin and Isoniazid.The Journal of molecular diagnostics : JMD · 2023Article
- In silico evaluation of WHO-endorsed molecular methods to detect drug resistant tuberculosis.Scientific reports · 2022Article
- Multiplex SuperSelective PCR Assays for the Detection and Quantitation of Rare Somatic Mutations in Liquid Biopsies.The Journal of molecular diagnostics : JMD · 2022Article
- Highly Sensitive Detection of Isoniazid Heteroresistance inInfection and drug resistance · 2022Article
- Xpert MTB/XDR: a 10-Color Reflex Assay Suitable for Point-of-Care Settings To Detect Isoniazid, Fluoroquinolone, and Second-Line-Injectable-Drug Resistance Directly from Mycobacterium tuberculosis-Positive Sputum.Journal of clinical microbiology · 2021Article
- Combination of Xpert MTB/RIF and MTBDRplus for Diagnosing Tuberculosis in a Chinese District.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- A Benchtop Automated Sputum-to-Genotype System Using a Lab-on-a-Film Assembly for Detection of Multidrug-ResistantAnalytical chemistry · 2020Article
- Isoniazid-resistant tuberculosis: A problem we can no longer ignore.PLoS medicine · 2020Article
- Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Extensively drug-resistant (XDR) tuberculosis (TB) cannot be easily or quickly diagnosed. We developed a rapid, automated assay for the detection of XDR-TB plus resistance to the drug isoniazid (INH) for point-of-care use. Using a simple filter-based cartridge with an integrated sample processing function, the assay identified a wide selection of wild-type and mutant sequences associated with XDR-TB directly from sputum. Four new large-Stokes-shift fluorophores were developed. When these four Stokes-shift fluorophores were combined with six conventional fluorophores, 10-color probe detection in a single PCR tube was enabled. A new three-phase, double-nested PCR approach allowed robust melting temperature analysis with enhanced limits of detection (LODs). Finally, newly designed sloppy molecular beacons identified many different mutations using a small number of probes. The assay correctly distinguished wild-type sequences from 32 commonly occurring mutant sequences tested in gyrA, gyrB, katG, and rrs genes and the promoters of inhA and eis genes responsible for resistance to INH, the fluoroquinolone (FQ) drugs, amikacin (AMK), and kanamycin (KAN). The LOD was 300 CFU of Mycobacterium tuberculosis in 1 ml sputum. The rate of detection of heteroresistance by the assay was equivalent to that by Sanger sequencing. In a blind study of 24 clinical sputum samples, resistance mutations were detected in all targets with 100% sensitivity, with the specificity being 93.7 to 100%. Compared to the results of phenotypic susceptibility testing, the sensitivity of the assay was 75% for FQs and 100% each for INH, AMK, and KAN and the specificity was 100% for INH and FQ and 94% for AMK and KAN. Our approach could enable testing for XDR-TB in point-of-care settings, potentially identifying highly drug-resistant TB more quickly and simply than currently available methods.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.